AbstractIntroduction: Preparation of tramadol HCl sustained release delivery system as an analgesic drug could improve its efficacy, reduce side effects and increase patient compliance.Objective: The aim of the present study was to prepare tramadol HCl loaded microspheres and coat them by solvent evaporation (ESE) method, in order to obtain an appropriate sustained release behavior and to prevent initial burst release.Materials and Methods: For this purpose, in the first stage, microspheres were prepared using ethyl cellulose by ESE method, and the effect of different variables such as the amount of drug and polymer as well as internal phase solvent volume on their physicochemical properties including particle size, encapsulation efficiency, surface morphology and drug release was studied. Also, the modified solvent evaporation method (MESE) was used for microspheres formation and comparison with ESE method.Results: Based on the results, the mean diameter of the microspheres prepared by solvent evaporation method was in the range of 80-173 μm, and encapsulation efficiency of 68-92 %. Release studies showed a burst effect of tramadol HCl from microspheres obtained from both MESE and ESE methods, which was mainly due to the presence of drug crystals on the surface of the particles. In order to eliminate this occurrence, primary microspheres were prepared and coated with ethyl cellulose using a one-step solvent evaporation method which resulted in microspheres with sustained release behavior without burst release.Conclusion: Preparation of coated tramadol HCl-loaded microspheres by solvent evaporation method could be considered as an appropriate technique to control the drug release rate and prevent the burst effect.Conflict of interest: non declared